No Smoke Without Fire: Cigarette Smoking Affects Drug Metaboiism Although the effect of cigarette smoking is difficult to distinguish from that of age

Cigarette smoke contains a large number of chemicals, the most important of which, from the point of view of effects on drug activity, are polycyclic aromatic hydrocarbons, as they are powerful hepatic microsomal enzyme inducers. Enzyme induction can cause adverse reactions by altering the steady-state concentrations of chronically administered drugs and this effect is likely to be greatest for drugs primarily cleared by hepatic metabolism. These include opiates, phenothiazines, barbiturates, anticoagulants, hypoglycaemic agents and antihypertensives.

The polycyclic hydrocarbons induce cytochrome P448 and aryl hydrocarbon hydroxylase (AHH) with different affinities for a given substrate. Considerable interindividual variation of aryl hydrocarbon hydroxylase activity has been identified in human liver, placenta, and lymphocytes, which partially explains the apparent selectivity of cigarette smoking on drug metabolism. Placental mono-oxygenase activity has been found to be sensitive to both active and passive smoke exposure.

A study with antipyrine [phenazone] found that smoking significantly increased antipyrine plasma elimination and accelerated clearance rates. A positive correlation was found between age and smoking effects. Metabolising capacity decreased with increasing age and the shortening of plasma half-jife was also less with increasing age.

Desmethyldiazepam was found to have a decreased plasma half-life and an increased plasma clearance in smokers compared with non-smokers. Chlorpromazine demonstrated a mean plasma concentration 24% lower and a mean AUC 36% lower in smokers than non-smokers. Possibly, because of the small sample size , this difference was not significant. A correlation was found between degree of drowsiness in patients taking chlorpromazine and their smoking habits.

Decreased plasma concentrations were found in smokers vs non-smokers taking clomipramine and phenacetin, while increased plasma clearance was demonstrated for diazepam, paracetamol [acetaminophen], propranolol and warfarin. It is thought that smoking may give rise to, or accentuate, the age-related reduction in steady-state concentrations of propranolol. While no difference in analgesic efficacy of codeine in smokers or non-smokers was demonstrated, the possibility that brain microsomal metabolism may be affected by smoking was suggested.

The mean plasma half-life of theophylline was found to be decreased in smokers but the apparent volume of distribution was similar for smokers and non-smokers. Another study in patients with a mean age of 75 years demonstrated a 40% higher theophylline clearance in smokers compared with non-smokers of that age. Luczynska, C and Wilson" K .. Methods and Findings in Experimental and Clinical Pharmacology 5.' 479 (Sep 1983)

2 tNPHARMA ® 17 Mar 1984 0156-2703/84/0317-0002/0$01.00/0 © ADtS Press